Lipoic acid metabolism and mitochondrial redox regulation

Ashley Solmonson, Ralph J. DeBerardinis

Research output: Contribution to journalReview article

19 Citations (Scopus)

Abstract

Lipoic acid is an essential cofactor for mitochondrial metabolism and is synthesized de novo using intermediates from mitochondrial fatty-acid synthesis type II, S-adenosylmethionine and iron–sulfur clusters. This cofactor is required for catalysis by multiple mitochondrial 2-ketoacid dehydrogenase complexes, including pyruvate dehydrogenase, -ketoglutarate dehydrogenase, and branched-chain ketoacid dehydrogenase. Lipoic acid also plays a critical role in stabilizing and regulating these multienzyme complexes. Many of these dehydrogenases are regulated by reactive oxygen species, mediated through the disulfide bond of the prosthetic lipoyl moiety. Collectively, its functions explain why lipoic acid is required for cell growth, mitochondrial activity, and coordination of fuel metabolism.

Original languageEnglish (US)
Pages (from-to)7522-7530
Number of pages9
JournalJournal of Biological Chemistry
Volume293
Issue number20
DOIs
StatePublished - Jan 1 2018

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Thioctic Acid
Metabolism
Pyruvate Dehydrogenase Complex
Oxidation-Reduction
Oxidoreductases
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
Multienzyme Complexes
S-Adenosylmethionine
Cell growth
Prosthetics
Catalysis
Pyruvic Acid
Disulfides
Reactive Oxygen Species
Fatty Acids
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lipoic acid metabolism and mitochondrial redox regulation. / Solmonson, Ashley; DeBerardinis, Ralph J.

In: Journal of Biological Chemistry, Vol. 293, No. 20, 01.01.2018, p. 7522-7530.

Research output: Contribution to journalReview article

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AB - Lipoic acid is an essential cofactor for mitochondrial metabolism and is synthesized de novo using intermediates from mitochondrial fatty-acid synthesis type II, S-adenosylmethionine and iron–sulfur clusters. This cofactor is required for catalysis by multiple mitochondrial 2-ketoacid dehydrogenase complexes, including pyruvate dehydrogenase, -ketoglutarate dehydrogenase, and branched-chain ketoacid dehydrogenase. Lipoic acid also plays a critical role in stabilizing and regulating these multienzyme complexes. Many of these dehydrogenases are regulated by reactive oxygen species, mediated through the disulfide bond of the prosthetic lipoyl moiety. Collectively, its functions explain why lipoic acid is required for cell growth, mitochondrial activity, and coordination of fuel metabolism.

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